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Tamoxifen Resistance and CYP2D6 Copy Numbers in Breast Cancer Patients

  • Motamedi, Sahar;Majidzadeh, Keivan;Mazaheri, Mahta;Anbiaie, Robab;Mortazavizadeh, Seyed Mohammad Reza;Esmaeili, Rezvan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6101-6104
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    • 2012
  • Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative $C_t$ (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.

Watch and Wait in Lebanese Chronic Lymphocytic Leukemia Patients: How Relevant is it?

  • Lutfallah, Antoine Abi;Kourie, Hampig Raphael;Eid, Roland;Farhat, Fadi;Ghosn, Marwan;Kattan, Joseph
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.215-217
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    • 2016
  • Background: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (W&W) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W&W strategy in Lebanese CLL patients. Materials and Methods: A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W&W strategy, different chemotherapeutic regimens and the indications for treatment. Results: Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was $39885/mm^3$ [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was $191255/mm^3$ [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W&W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W&W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade. Conclusions: This retrospective review of CLL clinical practice showed an important implementation of the W&W strategy with a long duration, especially in early stage cases with low RAI or Binet scores.

Genetic Analysis of SCN5A in Korean Patients Associated with Atrioventricular Conduction Block

  • Park, Hyoung-Seob;Kim, Yoon-Nyun;Lee, Young-Soo;Jung, Byung-Chun;Lee, Sang-Hee;Shin, Dong-Gu;Cho, Yong-Keun;Bae, Myung-Hwan;Han, Sang-Mi;Lee, Myung-Hoon
    • Genomics & Informatics
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    • v.10 no.2
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    • pp.110-116
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    • 2012
  • Recent several studies have shown that the genetic variation of SCN5A is related with atrioventricular conduction block (AVB); no study has yet been published in Koreans. Therefore, to determine the AVB-associated genetic variation in Korean patients, we investigated the genetic variation of SCN5A in Korean patients with AVB and compared with normal control subjects. We enrolled 113 patients with AVB and 80 normal controls with no cardiac symptoms. DNA was isolated from the peripheral blood, and all exons (exon 2-exon 28) except the untranslated region and exon-intron boundaries of the SCN5A gene were amplified by multiplex PCR and directly sequenced using an ABI PRISM 3100 Genetic Analyzer. When a variation was discovered in genomic DNA from AVB patients, we confirmed whether the same variation existed in the control genomic DNA. In the present study, a total of 7 genetic variations were detected in 113 AVB patients. Of the 7 variations, 5 (G87A-A29A, intervening sequence 9-3C>A, A1673G-H558R, G3578A-R1193Q, and T5457C-D1819D) have been reported in previous studies, and 2 (C48G-F16L and G3048A-T1016T) were novel variations that have not been reported. The 2 newly discovered variations were not found in the 80 normal controls. In addition, G298S, G514C, P1008S, G1406R, and D1595N, identified in other ethnic populations, were not detected in this study. We found 2 novel genetic variations in the SCN5A gene in Korean patients with AVB. However, further functional study might be needed.

Seedling Conditions for Kimchi Cabbage, Head Lettuce, Cabbage and Broccoli for a Riding-type Transplanter

  • Lim, Jung-Hyun;Park, Suh-young;Chae, Won-Byung;Kim, Sung-Kyeom;Choi, Seung-Kook;Yang, Eun-Young;Lee, Min-Ji;Park, Gyeong-Bin;Jang, Yoon-ah;Seo, Myeong-Hoon;Jang, Suk-Woo
    • Journal of Biosystems Engineering
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    • v.42 no.2
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    • pp.104-111
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    • 2017
  • Purpose: We have studied the necessary qualities of seedlings of some leafy vegetables for a riding-type two-row automatic transplanter. When seedlings are planted using a transplanter, long roots may be rounded in the bottom of the tray, and this can interfere with the separation of the seedlings. Uprightness related to leaf spread angle is an important quality for seedlings in mechanical planting. Methods: To select cultivars suitable for the transplanter, we compared varieties of Kimchi cabbage (Chukwang, Daetong, Whipalam and Namdo), head lettuce (Abi and Sensation), cabbage (YR Onnuri, YR Hogel, Harutama, and Ogane), and broccoli (Nicegreen and Earlyyou). To compare the effect of bed soil on root formation and growth, we used five types of soil: Chologi, Burger, Wonjomix, Bio, and Baroker with 2.6-3 L per tray. Growth increment and the degree of root formation were measured according to the RDA guidelines 25 days after sowing for Kimchi cabbage and head lettuce and 44 days after sowing for cabbage and broccoli. Conclusions: According to the plug tray, the optimum seedling age in both 128- and 200-hole trays was 28 days for Kimchi cabbage and 44 days for cabbage and broccoli. Head lettuce took 35 days in 128-hole trays and 31 days in 200-hole trays. Burger soil was most effective for root formation and growth of the four kinds of leafy vegetables; it appeared that smaller soil volume led to faster root formation.

Studies on Proteolytic and Fibrinolytic Activity of Bacillus subtilis JM-3 Isolated from Anchovy Sauce (멸치액젓으로부터 분리한 Bacillus subtilis JM-3의 단백질 분해활성과 혈전 용해 활성에 관한 연구)

  • Lee, Sang-Soo;Kim, Sang-Moo;Park, Uk-Yeon;Kim, Hee-Yun;Shin, Il-Shik
    • Korean Journal of Food Science and Technology
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    • v.34 no.2
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    • pp.283-289
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    • 2002
  • This study was performed to search for potential microorganism that has rapid fermenting and physiological function from anchovy sauce. We isolated three bacterial strains, JM-1, JM-2, and JM-3 with proteolytic and fibrinolytic activity from anchovy sauce. Among the 3 bacterial strains, JM-3 showed the strongest proteolytic and fibrinolytic activity. Bacterial strain JM-3 was gram-positive rod, motile and formed endospore. The 16S rRNA of bacterial strain JM-3 was amplified by PCR and then its sequence was determined by ABI 310 genetic analyzer. The 16S rRNA sequence of bacterial strain JM-3 was compared to BLAST DNA database and identified to Bacillus subtilis with 99% of homology. The optimum temperature, pH and NaCl concentration for growth of B. subtilis JM-3 were $40^{\circ}C$, 5.0 and 0%, respectively. The optimum temperature, pH and NaCl concentration for proteolytic and fibrinolytic enzyme production of B. subtilis JM-3 were same as optimum conditions for growth. At 20% of NaCl concentration which is common NaCl concentration of fish sauce, B. subtilis JM-3 showed about 60% of proteolytic and fibrinolytic activity of 0% NaCl concentration. From above results, we found that B. subtilis JM-3 will be able to used for starter of functional fish sauce.

Impact of Student Assessment Activities on Reflective Thinking in High School Argument-Based Inquiry (고등학교 논의기반 탐구 과학수업에서 학생 평가활동이 반성적 사고에 미치는 영향)

  • Lee, Seonwoo;Nam, Jeonghee
    • Journal of The Korean Association For Science Education
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    • v.36 no.2
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    • pp.347-360
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    • 2016
  • This study focused on the use of student assessment activities to investigate the impact on reflective thinking in Argument-based Inquiry. The participants of the study were 166 10th grade students (six classes). Over one semester, students participated in five ABI programs that we developed. The experimental group (84 students) was taught Argument-Based Inquiry with students' self and peer assessment activities. The comparative group (82 students) was taught without the activities. We analyzed students' reflective writing to investigate how the student assessment activities influenced the students' reflective thinking. We also used the interviews and surveys to examine the validity of student assessment activities. According to analysis of the reflective writing, the experimental group had a significantly higher mean score than the comparative group in the 3rd and 5th writing. The ratio of students who showed a metacognitive level of reflection with regard to analysis of inquiry process, understanding of learning, and change of thinking increased in both groups, but the experimental group's ratio was higher than the comparative group's. The result of analysis of the reflective practice showed that the ratio of the experimental group's students who reached the metacognitive level of reflection in their writing increased, while the comparative group's decreased. Therefore, we conclude that student assessment activities can create a learning environment that facilitates student participation, increases the students' engagement in the learning process, and can be used as a tool to scaffold learning.

Management of Diabetic Mellitus in Low-income Rural Patients (일개 농촌지역 저소득층 당뇨병환자의 관리 상태)

  • Kim, Hye-Yeon;Yun, Woo-Jun;Shin, Min-Ho;Kweon, Sun-Seong;Ahn, Hye-Ran;Choi, Seong-Woo;Lee, Young-Hoon;Cho, Dong-Hyeok;Rhee, Jung-Ae
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.5
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    • pp.315-322
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    • 2009
  • Objectives : Knowledge about the management status of diabetic melitus (DM) is essential to improve diabetic management. Moreover, low income is associated with poor adherence to treatment and increased mortality. This study was performed to evaluate the management status of DM in low-income patients in a rural area. Methods : We enrolled 370 patients with type 2 DM living in Gokseong county, JeollaNamdo. A well-trained examiner measured the height, weight, waist circumference, blood pressure, total cholesterol, triglyceride, high density lipoprotein cholesterol, fasting blood sugar and glycosylated hemoglobin (HbA1c) levels. Carotid ultrasonography was used to measure carotid artery carotid artery intima media thickness (IMT) and plaque. anklebrachial index (ABI) was used to evaluate peripheral artery disease. A fundoscopic examination was performed to evaluate diabetic retinopathy. A history of diabetes complications and health-related questionnaires were also completed. Results : The age of diabetic subjects was 68.7$\pm$8.7 years and the duration of diabetes was 8.9$\pm$8.2 years. Most (63.5%) had hypertension, and 45.7% had triglycerides below 150 mg/dl, 38.1% had low density lipoprotein cholesterol (LDL) cholesterol below 100 mg/dl, 48.7% had urine albumin to creatinine ratio (UACR) below 30 mg/g. Less than half (45.9%) achieved the goal of HbA1c less than 7% suggested by the American Diabetes Association (ADA). 10.6% had peripheral vascular disease, 11.9% had retinopathy, and 60.8% had chronic kidney disease. Conclusions : DM management in low income patients is very poor and requires further work to improve.

No Associations between Schizophrenia and D22S280 Marker on Synapsin III Gene in Korean Males (한국인 남자에서 Synapsin III 유전자의 D22S280 표지자와 정신분열병의 연합연구)

  • Lee, Yu-Sang;Park, Chong-Won;Lee, Seung-Yeoun;Lee, Suk-Jin;Park, Yong-Bum;Shin, Yoon-Sik;Yoo, Jang-Keun;Hong, Kyung Sue;Yang, Byung-Hwan
    • Korean Journal of Biological Psychiatry
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    • v.13 no.4
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    • pp.260-266
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    • 2006
  • Objectives : Synapsin III near VCFS region on chromosome 22q affects. It could be an interesting candidate gene for schizophrenia. D22S280 is a highly polymorphic genetic marker residing in synapsin III. We examined association of D22S280 marker on synapsin III with Korean patients with schizophrenia. Methods : The subjects were 46 male Korean patients with schizophrenia and 60 male normal controls. Using polymerase chain reaction, gel electrophoresis, ABI 310 genetic analyzer, and GeneScan Collection 3.1 software, we confirmed genotypes of D22S280 marker. We examined Hardy-Weinberg equilibrium and case-control association using SAS/Genetic 9.1.3. Results : Genotypes of both schizophrenia and control groups were in Hardy-Weinberg equilibrium. We could not find any significant statistical differences in allele-wise(${\chi}^2$=10.4, df=6, p=0.098) and genotype-wise (${\chi}^2$=22.1 df=19, p=0.258) analyses of D22S280 marker between schizophrenia and normal controls. Individual allele analyses with df=1 showed significant differences in A1(p=0.025) and A7(p=0.034) allele, which were not significant following Bonferroni corrections(A1:p=0.177, A7:p=0.235). Conclusion : We couldn't find any association between schizophrenia and the synapsin III gene. Given the small number of subjects studied, further investigations are needed.

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Short Bowel Syndrome as the Leading Cause of Intestinal Failure in Early Life: Some Insights into the Management

  • Goulet, Olivier;Nader, Elie Abi;Pigneur, Benedicte;Lambe, Cecile
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.4
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    • pp.303-329
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    • 2019
  • Intestinal failure (IF) is the critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children. Severe IF requires parenteral nutrition (PN). Pediatric IF is most commonly due to congenital or neonatal intestinal diseases or malformations divided into 3 groups: 1) reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis; 2) abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development; 3) extensive motility dysfunction such as chronic intestinal pseudo-obstruction syndromes. The leading cause of IF in childhood is the SBS. In clinical practice the degree of IF may be indirectly measured by the level of PN required for normal or catch up growth. Other indicators such as serum citrulline have not proven to be highly reliable prognostic factors in children. The last decades have allowed the development of highly sophisticated nutrient solutions consisting of optimal combinations of macronutrients and micronutrients as well as guidelines, promoting PN as a safe and efficient feeding technique. However, IF that requires long-term PN may be associated with various complications including infections, growth failure, metabolic disorders, and bone disease. IF Associated Liver Disease may be a limiting factor. However, changes in the global management of IF pediatric patients, especially since the setup of intestinal rehabilitation centres did change the prognosis thus limiting "nutritional failure" which is considered as a major indication for intestinal transplantation (ITx) or combined liver-ITx.

CD8+ T Cell-mediated Immunity Induced by Heterologous Prime-boost Vaccination Based on DNA Vaccine and Recombinant Vaccinia Virus Expressing Epitope (Epitope발현 DNA Vaccine과 Recombinant Vaccinia Virus를 이용한 Heterologous Prime-boost Vaccination에 의하여 유도되는 CD8+ T 세포 매개성 면역)

  • Park, Seong-Ok;Yoon, Hyun-A;Aleyas, Abi George;Lee, John-Hwa;Chae, Joon-Seok;Eo, Seong-Kug
    • IMMUNE NETWORK
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    • v.5 no.2
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    • pp.89-98
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    • 2005
  • Background: DNA vaccination represents an anticipated approach for the control of numerous infectious diseases. Used alone, however, DNA vaccine is weak immunogen inferior to viral vectors. In recent, heterologous prime-boost vaccination leads DNA vaccines to practical reality. Methods: We assessed prime-boost immunization strategies with a DNA vaccine (minigene, $gB_{498-505}$ DNA) and recombinant vaccinia virus $(vvgB_{498-505})$ expressing epitope $gB_{498-505}$ (SSIEF ARL) of CD8+ T cells specific for glycoprotein B (gB) of herpes simplex virus (HSV). Animals were immunized primarily with $gB_{498-505}$ epitope-expressing DNA vaccine/recombinant vaccinia virus and boosted with alternative vaccine type expressing entire Ag. Results: In prime-boost protocols using vvgBw (recombinant vaccinia virus expressing entire Ag) and $vvgB_{498-505}$, CD8+ T cell-mediated immunity was induced maximally at both acute and memory stages if primed with vvgBw and boosted with $vvgB_{498-505}$ as evaluated by CTL activity, intracellular IFN-staining, and MHC class I tetramer staining. Similarly $gB_{498-505}$ DNA prime-gBw DNA (DNA vaccine expressing entire Ag) boost immunization elicited the strongest CD8+ T cell responses in protocols based on DNA vaccine. However, the level of CD8+ T cell-mediated immunity induced with prime-boost vaccination using DNA vaccine expressing epitope or entire Ag was inferior to those based on vvgBw and $vvgB_{498-505}$. Of particular interest CD8+ T cell-mediated immunity was optimally induced when $vvgB_{498-505}$ was used to prime and gB DNA was used as alternative boost. Especially CD7+ T cell responses induced by such protocol was longer lasted than other protocols. Conclusion: These facts direct to search for the effective strategy to induce optimal CD8+ T cell-mediated immunity against cancer and viral infection.